1. Field of the Invention
The present invention relates to a novel process for the preparation of 2,5-diamino!-4-hydroxy-azahexane derivatives and to novel intermediates for the preparation thereof. The 2,5-diamino!-4-hydroxy-azahexane derivatives serve as starting materials in the preparation of antiviral compounds or themselves exhibit antiviral activity.
2. Reference to the Prior Art
The present invention relates to the preparation of starting materials with a view to the preparation of end products of the 2,5-diamino!-4-hydroxy-azahexane type that are suitable for the treatment of viral diseases, for example retroviral diseases, such as AIDS. Such antiviral end products are to be found, for example, in European Patent Applications EP 0 521 827 and EP 0 604 368 and in PCT Applications WO 93/18006, WO 95/07269 and WO 94/19332, those Applications also mention the test systems that enable the antiviral activity of the antiviral end products to be checked. Some of the starting materials also exhibit the pharmaceutical action mentioned.
The aim of the present invention is to provide an entirely novel process for the preparation of starting materials for the preparation of such compounds and to provide novel intermediates for that purpose.
The principal aims include to use simple starting materials, to avoid extreme reaction conditions, for example low-temperature reactions, to avoid intermediates that are difficult to prepare or handle (especially on a large scale), such as epoxides or Grignard reagents, to provide a novel method of obtaining the starting materials for the antiviral end products and/or especially to allow reaction steps to be carried out stereoselectively.
As a result of the novel reaction route described below, which yields the starting materials for the antiviral pharmaceutical active ingredients in a surprising manner, for example by means of a surprising acyl migration at a certain reaction step, one or more of the mentioned aims are unexpectedly achieved and also individual stereoisomers of compounds of formula I can be prepared in pure form and on a large scale, one advantage of the reaction route being a high degree of safeguarding against racemisation.
The intermediates of formula I can be utilised directly as pharmaceutically active compounds or can be converted into pharmaceutically active compounds by removal of protecting groups and acylation of radicals carrying R.sub.1 and/or R.sub.4 as protecting groups and, if necessary, further reactions, for example as described in European Patent Applications EP 0 521 827 and EP 0 604 368 and in PCT Applications WO 93/18006, WO 95/07269 and WO 94/19332, or in an analogous manner.